Background: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy developed for targeted skeletal and cardiac muscle expression of micro-dystrophin, a shortened, functional, dystrophin protein.
Objective: This three-part, Phase 2 clinical trial (NCT03769116) evaluates the safety and efficacy of systemic gene transfer of delandistrogene moxeparvovec in patients with Duchenne muscular dystrophy (DMD).
Results: Part 1 is a 48-week, randomized, double-blind, placebo-controlled period. Part 2 is a 48-week period in which patients, randomized to placebo in Part 1, receive delandistrogene moxeparvovec. Part 3 is an open-label, follow-up period (?212 weeks).
Participants from Part 1 (N=41) were 4–7-year-old ambulatory boys with confirmed DMD mutation between exons 18–58 and stable steroid dosing. The intended dose was 2.0×1014 vg/kg (supercoiled qPCR, linear plasmid standard equivalent of 1.33×1014 vg/kg).
Randomization was stratified by age (4–5 and 6–7 years). Primary endpoints were change from baseline in micro-dystrophin expression (western blot; baseline to Week 12) and North Star Ambulatory Assessment (baseline to Week 48). Safety endpoints included serious adverse events and treatment-emergent adverse events.
One-year functional results from Part 1 have been presented previously. Full analyses from Parts 1 and 2 will be presented, including 2-year functional and safety data from patients who received delandistrogene moxeparvovec in Part 1; 1-year functional and safety data from patients who received delandistrogene moxeparvovec in Part 2; and expression data for all patients 12 weeks post-delandistrogene moxeparvovec infusion and 60 weeks post-infusion for those dosed in Part 1.
Conclusions: Results suggest that delandistrogene moxeparvovec has a biological effect that may be clinically relevant in people with DMD. Results reinforce a potentially favorable benefit-risk profile.
This study is funded by Sarepta Therapeutics, Inc.